Method for targeting cells involved in sclerotic and/or fibrotic diseases

Abstract

A compound includes a carrier molecule wherein the carrier molecule is linked to a further molecule, wherein the further molecule is at least one cyclic peptide in which the cyclic peptide portion thereof contains at least one sequence encoding a cell receptor recognizing peptide (RRP) and with the proviso that the compound is not a naturally occurring receptor agonist or antagonist. Preferably, the RRP is a receptor specific for Hepatic Stellate Cells (HSC) or a receptor that is up-regulated on HSC during disease. The RFP may be chosen from among a PDGF receptor, a collagen type VI receptor, cytokine receptor(s) such as TGBβ, INFα and interleukinβ. The cyclic portion of the peptide can contain at least one amino acid sequence RGD or KPT. The compounds can be used as an active targeting ingredient for manufacturing a pharmaceutical composition for therapy, prophylaxis or diagnosis of a disease chosen from fibrotic disease, sclerotic disease, and chronic or acute inflammatory processes including glomeruloscherosis, interstitial fibrosis, lung fibrosis, atherosclerosis, rheumatoid arthritis, Crohns disease, colitis ulcerosa, glomerulonephritis and sepsis, and particularly for targeting HSC. Pharmaceutical compositions contain the above-compound(s).

1. A method for targeting cells for diagnostic or drug-delivery involved in sclerotic and/or fibrotic diseases, and in which cells the Insulin Growth Factor II/mannose-G-phosphate receptor (IGFII/M6P receptor) is upregulated during disease, in a subject in need thereof or in a tissue sample of a subject, using, in a pharmaceutically acceptable amount and form a carrier molecule that comprises human serum albumin (HSA) or bovine serum albumin (BSA), wherein said carrier molecule is linked to at least one further molecule, said further molecule being mannose-6-phosphate, wherein at least 10 to 28 molecules of mannose-6-phosphate are linked to said carrier. 
     
     
       2. A method according to  claim 1 , wherein the cells are Hepatic Stellate Cells (HSC). 
     
     
       3. A method according to  claim 1 , wherein the carrier molecule comprises additional drugs or chemicals linked thereto. 
     
     
       4. A method according to  claim 1 , wherein the cells involved in a sclerotic and/or a fibrotic disease are cells involved in a disease selected from the group consisting of liver fibrosis, kidney fibrosis, lung fibrosis, atherosclerosis and chronic or acute inflammatory processes, Crohn's disease, colitis ulcerosa, glomerulonephritis, sepsis and tumor-cell proliferation associated pathology, fibroblast proliferation associated pathology, endothelial cell proliferation associated pathology and osteoblast proliferation associated pathology. 
     
     
       5. The method according to  claim 1 , wherein said carrier comprises human serum albumin (HSA). 
     
     
       6. The method according to  claim 1 , wherein said carrier comprises bovine serum albumin (BSA).